A5049996114- PARP inhibition in cancer therapy
- Retinal Development and Disorders
- Calcium signaling and nucleotide metabolism
- Viral Infections and Immunology Research
- Retinal Diseases and Treatments
- RNA Research and Splicing
- Steroid Chemistry and Biochemistry
- Pharmacogenetics and Drug Metabolism
- Retinoids in leukemia and cellular processes
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- Plant Virus Research Studies
- Photochromic and Fluorescence Chemistry
- Hormonal Regulation and Hypertension
- RNA Interference and Gene Delivery
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Nanopore and Nanochannel Transport Studies
- Pediatric Hepatobiliary Diseases and Treatments
- Photosynthetic Processes and Mechanisms
- Advanced biosensing and bioanalysis techniques
- Algal biology and biofuel production
- Memory and Neural Mechanisms
Johns Hopkins University
2020-2024
Ahvaz Jundishapur University of Medical Sciences
2024
Case Western Reserve University
2015-2023
Johns Hopkins Medicine
2021
Cleveland Eye Clinic
2017
Cleveland Clinic
2017
Louis Stokes Cleveland VA Medical Center
2017
Cleveland Clinic Lerner College of Medicine
2017
Biotechnology Research Center
2009-2011
Tehran University of Medical Sciences
2007-2011
Macrodomain (MD), a highly conserved protein fold present in subset of plus-strand RNA viruses, binds to and hydrolyzes ADP-ribose (ADPr) from ADP-ribosylated proteins. ADPr-binding by the alphavirus nonstructural 3 (nsP3) MD is necessary for initiation virus replication neural cells, whereas hydrolase activity facilitates complex amplification. To determine importance these activities pathogenesis encephalomyelitis, mutations were introduced into nsP3 Sindbis (SINV), effects on ADPr binding...
Emixustat is a visual cycle modulator that has entered clinical trials as treatment for age-related macular degeneration (AMD). This molecule been proposed to inhibit the isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production retinaldehyde condensation byproducts may be involved in AMD pathology. Previously, we reported all-trans-retinal (atRAL) directly cytotoxic certain primary amine compounds transiently sequester atRAL via Schiff base formation ameliorate...
Poly(ADP-ribose) (PAR) is a homopolymer of adenosine diphosphate ribose that added to proteins as posttranslational modification regulate numerous cellular processes. PAR also serves scaffold for protein binding in macromolecular complexes, including biomolecular condensates. It remains unclear how achieves specific molecular recognition. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) evaluate flexibility under different cation conditions. We demonstrate that,...
Huntington disease (HD) is a genetic neurodegenerative caused by cytosine, adenine, guanine (CAG) expansion in the
Carotenoid cleavage oxygenases (CCOs) are non-heme iron enzymes that catalyze scission of alkene groups in carotenoids and stilbenoids to form biologically important products. CCOs possess a rare four-His center whose resting-state structure interaction with substrates incompletely understood. Here, we address this knowledge gap through comprehensive structural spectroscopic study three phyletically diverse CCOs. The crystal fungal stilbenoid-cleaving CCO, CAO1, reveals strong similarity...
Visual function in vertebrates critically depends on the continuous regeneration of visual pigments rod and cone photoreceptors. RPE65 is a well-established retinoid isomerase pigment epithelium that regenerates rhodopsin during cycle; however, its contribution to remains obscure. In this study, we use potent selective inhibitors rod- cone-dominant animal models discern role enzyme cone-mediated vision. We confirm retinylamine emixustat-family compounds selectively inhibit over DES1,...
Modulators of the visual cycle have been developed for treatment various retinal disorders. These agents were designed to inhibit retinoid isomerase [retinal pigment epithelium-specific 65 kDa protein (RPE65)], rate-limiting enzyme cycle, based on idea that attenuation regeneration could reduce formation toxic conjugates. Of these agents, certain ones contain primary amine groups can also reversibly form retinaldehyde Schiff base adducts, which contributes their protective activity. Direct...
Abstract BACKGROUND: A large number of bacterial, fungal and microalgal species are able to bio‐transform steroid compounds. Among them, fungi from the Mucor genus have been shown mediate hydroxylation, oxidation, desaturation by double bond formation epoxidation various substances. racemocus has not studied for its ability modify androst‐1,4‐dien‐3,17‐dione, a pharmaceutically important precursor. RESULTS: The filamentous fungus M. racemosus was applied bioconversion...
Ileal bile acid binding protein (I-BABP, gene name FABP6) is a component of the recycling system, expressed in ileal enterocyte. The physiological role I-BABP has been hypothesized to be either an intracellular buffering agent protect against excess acids or separately as modulator controlled transcription. We investigated mouse (mI-BABP) understand function this family. Here, we studied energetics and site selectivity with using combination isothermal calorimetric analysis NMR spectroscopy....
In the eye, isomerization of all-trans-retinal to 11-cis-retinal is accomplished by a metabolic pathway termed visual cycle that critical for vision. RPE65 essential trans–cis isomerase this pathway. Emixustat, retinoid-mimetic inhibitor, was developed as therapeutic modulator and used treatment retinopathies. However, pharmacokinetic liabilities limit its further development including: (1) deamination γ-amino-α-aryl alcohol, which mediates targeted inhibition, (2) unwanted long-lasting...
Abstract Toxin-antitoxin (TA) systems are broadly distributed, yet poorly conserved, genetic elements whose biological functions unclear and controversial. Some TA may provide bacteria with immunity to infection by their ubiquitous viral predators, the bacteriophage. To identify that protect E. coli MG1655 against phage, we searched for those frequently encoded near known phage defense genes in bacterial genomes. Two of tested strong protection homologs DarTG, a recently discovered family...
Non-alcoholic fatty liver disease (NAFLD) is a general term encompassing many conditions from simple to cirrhosis and hepatocellular carcinoma. In this research, we aimed investigate the effect of antioxidant protocatechuic acid (PCA) in preventing development induced by high-fat diet (HFD) male mice. Mice (NMRI) were randomly divided into five groups. The groups as follows: control received standard diet, HFD 20 ml/kg HFD, containing PCA 200 mg/kg/20 ml PCA, fenofibrate (FENO) 150 FENO,...
SUMMARY ADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization turnover. Here we show influenza A virus infection causes rapid dramatic upregulation of global inhibits viral replication. Mass spectrometry defined for the first time ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 sites on ∼1,080 host proteins,...
Poly(ADP-ribose) (PAR) is a homopolymer of adenosine diphosphate ribose that added to proteins as post-translational modification regulate numerous cellular processes. PAR also serves scaffold for protein binding in macromolecular complexes, including biomolecular condensates. It remains unclear how achieves specific molecular recognition. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) evaluate flexibility under different cation conditions. We demonstrate that,...
Abstract Huntington disease (HD) is a genetic neurodegenerative caused by CAG expansion in the Huntingtin (HTT) gene, translating to an expanded polyglutamine tract huntingtin protein. Age at onset correlates repeat length but varies decades between individuals with identical lengths. Genome-wide association studies link HD modification DNA repair and mitochondrial health pathways. Clinical show elevated damage HD, even premanifest stage. A major node influencing PARP pathway. Accumulation...
Poly(ADP-ribose) (PAR) is an RNA-like polymer that regulates increasing number of biological processes. Dysregulation PAR implicated in neurodegenerative diseases characterized by abnormal protein aggregation, including Amyotrophic Lateral Sclerosis (ALS). forms condensates with FUS, RNA-binding linked ALS, through unknown mechanism. Here, we demonstrate a strikingly low concentration (1 nM) sufficient to trigger condensation FUS near its physiological µM), which three orders magnitude lower...